Alveolar type II cells are specialized epithelial cells that line the alveolus and synthesize and secrete pulmonary surface active material. Type II cells are thought to be the stem cell for epithelium and proliferation of type II cells is critical for the restoration of gas exchange units after alveolar injury. The hypothesis, on which this project is based, is that for the functions of type II cells are important in our ultimate understanding of interstitial lung disease. In addition, we hypothesize that the functional state of type II cells can be determined in part by analysis of individual components of surfactant in lavage. We plan to analyze the 34 kd apoprotein (apoprotein A) and the phospholipids in lavage from patients with idiopathic pulmonary fibrosis and controls and from animals treated with bleomycin. We will develop methods of maintaining human and rat type II cells in a differentiated state in primary culture. This aim is very important for discovering the cellular regulation of different components of surfactant. Specifically, we want to determine if the 34 kd apoprotein, saturated phosphatidylcholine, and phosphatidylglycerol are independently regulated in type II cells from adult animals. We plan to develop methods for isolating hyperplastic type II cells to see if these cells are responsible for the alteration in surfactant lipids found in patients with ILD. Finally, we will test to see if there are growth factors for type II cells in lavages from patients or animals with interstitial lung disease. The proposed studies will focus on the role of parenchymal lung cells in the development of interstitial lung disease.